ferric derisomaltose (Rx)

1-10%

Hypophosphatemia (serum phosphate <2 mg/dL) (3.5%)

Nausea (1.2%)

Rash (1%)

Postmarketing Reports

Cardiac disorders: Tachycardia

Gastrointestinal disorders: Abdominal pain, nausea and vomiting, constipation, diarrhea

General disorders and administration site conditions: Fatigue, pyrexia, chest pain, chills, Fishbane reaction, extravasation, influenzalike symptoms, injection site reactions

Immune system disorders: Anaphylactic/anaphylactoid reaction, hypersensitivity

Investigations: Hepatic enzymes increased

Musculoskeletal and connective tissue disorders: Back pain, muscle spasms, arthralgia, myalgia

Nervous system disorders: Dizziness, headache, paresthesia, dysgeusia, seizure, loss of consciousness, syncope

Psychiatric disorders: Anxiety

Respiratory, thoracic, and mediastinal disorders: Dyspnea, cough

Skin and subcutaneous tissue disorders: Erythema, urticaria, skin discoloration, rash, pruritus, sweating

Vascular disorders: Hypertension, hypotension, flushing, phlebitis

Extravasation at the injection site that may lead to irritation of the skin and potentially long-lasting brown discoloration at the site of injection has also been reported

Contraindications

Hypersensitivity to ferric derisomaltose or any of its components

Cautions

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, reported

Excessive therapy with parenteral iron can lead to excess iron storage and possibly iatrogenic hemosiderosis or hemochromatosis; monitor hematologic response (hemoglobin and hematocrit) and iron parameters (serum ferritin and transferrin saturation) during therapy; do not administer to patients with iron overload

Pregnancy

There are no available data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Published studies on the use of IV iron products in pregnant women have not reported an association with adverse developmental outcomes; these studies cannot exclude the absence of any drug-related risk during pregnancy because the studies were not designed to assess for the risk of major birth defects

Animal data

• Iron complexes have been reported to be teratogenic and embryocidal in noniron-depleted pregnant animals
• Findings in animals may be due to iron overload and may not be applicable to patients with iron deficiency
• Animal reproduction studies of ferric derisomaltose administered to rats and rabbits during organogenesis caused adverse developmental outcomes including structural abnormalities and embryofetal mortality at doses ~0.09 and 0.4 times the maximum recommended human dose (MRHD) of 1000 mg, respectively, based on body surface area
• Administered intravenously to pregnant rabbits during organogenesis, from GD7 to GD20, at doses of 11, 25 and 43 mg Fe/kg/day; the dose of 43 mg Fe/kg/day (approximately 0.8 times the MRHD of 1000 mg, based on BSA) resulted in increased maternal mortality, abortion, and premature delivery, and increased postimplantation loss
• Adverse developmental findings at this dose included fetal mortality, reduced fetal weights, and fetal developmental variations and malformations (including domed head, cleft palate, microglossia, hydrocephaly, small brain); fetal malformations and reduced fetal weights were also noted in the 25 mg Fe/kg/day group (approximately 0.5 times the MRHD based on BSA)

Clinical considerations

• Untreated iron deficiency anemia in pregnancy is associated with adverse maternal outcomes (eg, postpartum anemia)
• Adverse pregnancy outcomes associated with iron deficiency anemia include increased risk for preterm delivery and low birth weight
• Risks to fetus associated with maternal severe hypersensitivity reactions
• Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products which may cause fetal bradycardia, especially during second and third trimester

Lactation

Available data on use in lactating women demonstrate that iron is present in breast milk

Data do not inform the potential exposure of iron for the breastfed child or the effects on milk production

Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for ferric derisomaltose in addition to any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition

Clinical considerations

• Monitor breastfed children for gastrointestinal toxicity (constipation, diarrhea)

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Ferric derisomaltose is a complex of iron (III) hydroxide and derisomaltose, an iron carbohydrate oligosaccharide that releases iron

Iron binds to transferrin for transport to erythroid precursor cells to be incorporated into hemoglobin

Absorption

Peak plasma concentration: 408 mcg/mL (single 1000-mg dose)

AUC: 17,730 mcg⋅hr/mL (single 1000-mg dose)

Serum ferritin peaks ~7 days after an IV dose and slowly returns to stable levels after about 4 weeks

Distribution

Circulating iron is removed from plasma by cells of the reticuloendothelial system

Iron is bound to the available protein moieties to form hemosiderin or ferritin, the physiological storage forms of iron, or to a lesser extent, to the transport molecule transferrin

Elimination

Half-life: 27 hr (measured by serum total iron)

Owing to the size of the complex, ferric derisomaltose is not excreted by the kidneys

Small quantities of iron are excreted in urine and feces

IV Incompatibilities

Compatibility with other drugs has not been established

Do not mix with or physically add to solutions containing other drugs

IV Preparation

Visually inspect vial for particulate matter and discoloration before administration; product contains no preservatives

Each vial is single-dose only; discard unused portion

Withdraw appropriate volume of ferric derisomaltose and dilute in 100-500 mL of 0.9% NaCl

Final diluted concentration should be >1 mg iron/mL

IV Administration

Only administer when personnel and therapies are immediately available for treatment of serious hypersensitivity reactions

Infuse IV over at least 20 min

Extravasation of ferric derisomaltose

• May cause brown discoloration at the extravasation site, which may be long lasting
• Monitor for extravasation
• If extravasation occurs, discontinue administration at that site

Storage

Unused vials: Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

Diluted solutions: Store at room temperature for up to 8 hr